In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

[Itraconazole-induced hypokalemia in a patient with pulmonary aspergilloma].

An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary aspergilloma. A new azole antifungal agent, D 0870, was administered to the patient for 7 days orally, and itraconazole (400 mg/day) was started on March 5, 1997. After 1 month of chemotherapy, facial and pretibial edema were observed and the patient's serum potassium concentration decreased to 2.5 mEq/l. A chest radiograph disclosed cardiomegaly with cardiac effusion and right pleural effusion on admission. The serum potassium concentration rose after the cessation of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks after admission. Although reports of hypopotassemia induced by ITCZ are rare, we concluded that blood concentrations should be monitored more carefully when treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.

Topical treatment of pulmonary aspergilloma by antifungals. Relationship between duration of the disease and efficacy of therapy.

Twelve patients with aspergilloma were treated with intracavitary or endobronchial administration of antifungals. Patients with successful therapy had significantly shorter mean duration of the disease course (3.6 months) than the less effective group (44.4 months, p < 0.01). Minimal inhibitory concentrations of antifungal agents against isolated strains of aspergilli were considerably lower than estimated intracavitary concentrations of the antifungals. A pathologic examination suggested that the old mycetoma was for the most part comprised of dead mycelial cells, against which antifungal agents were not effective. However, clinical improvement was obtained, regardless of the roentgenographic improvement. Our study suggested that early diagnosis and therapy are recommended to achieve better therapeutic effect.